1. Field of the Invention
This invention relates to a new immunosuppressant agent, "demethimmunomycin" (L-683,742: also described as 31-desmethoxy-31-hydroxy-L-683,590), a novel fermentation process for its production, utilizing the microorganism Actinoplanacete M (MA 6559), ATCC No. 53771. The process involves culturing the microorganism in the presence of L-683,590 under conditions which demethylates the C.sub.31 methoxy group of L-683,590. Also disclosed is a method of their use in a human host for treatment of autoimmune diseases, infectious diseases and/or prevention of organ transplant rejections.
2. Brief Description of Disclosures in the Art
In 1983, the US FDA licensed cyclosporin, and extremely effective anti-rejection drug that revolutionized the field of organ transplant surgery. The drug acts by inhibiting the body's immune system from mobilizing its vast arsenal of natural protecting agents to reject the transplant's foreign protein.
As effective as the drug is in fighting transplantation rejection, it suffers drawbacks in causing kidney failure, liver damage and ulcers which in many cases can be very severe.
EPO Publication No. 0184162 to Fujisawa, describes a new macrolide immunosuppressant FK-506 which is reputed to be 100 times more effective than cyclosporin. The macrolide is produced by fermentation of a particular strain of Strentomyces tsukubaensis. Also described is the closely related macrolide immunosuppressant FK-520, produced by S. hygroscopicus subsp. yakushimaensis.
U.S. Pat. No. 3,244,592 to T. Arai describes the culturing of Strerptomyces hygroscopicus var, ascomyceticus to produce the antifungal "ascomycin".
There is, however, no description in the literature of the production of any immunosuppressive agents, which substantially lack the side effects of cyclosporin.
Newer, safer drugs exhibiting less side effects are constantly being searched for in the field.